The primary objective is to evaluate and compare the acute and chronic effects of four new potentially useful hypolipidemic drugs: clofibrate, oxandrolone, norethindrone, and halofenate. Their potency as plasma and liver lipid-lowering agents will be determined in suitable animal models. To define the mechanisms and sites of action of these compounds, their effects on plasma post-heparin lipolytic and tissue lipoprotein lipase (LPL) activities of adipose tissue, heart and skeletal muscle will be measured. The influence of the drugs on LPL then will be correlated with drug-induced changes in: (1) the ultrastructure of adipose tissue, heart, skeletal muscle, liver, and intestine; and (2) lipoprotein synthesis in the liver and intestine as determined in cannulated intact animals and perfused livers. Other parameters also will be evaluated for potentially adverse drug effects: (1) pentobarbital sleeping times (drug interactions and metabolism); (2) total liver microsomal proteins (drug metabolism and alterations in the endoplasmic reticulum); (3) bile volumes and composition (hepatobiliary function). Drug-induced alterations in tissue fine structure of liver, intestine, adipose tissue, and muscle resulting from acute and chronic drug administration will be quantitated porphometrically and evaluated for real or potential toxicity. Defining the efficacy, mode of action, adverse and/or toxic effects of these drugs should facilitate their optimal therapeutic use and increase our understanding of lipoprotein metabolism.